Pyrrolidone carboxylic acid and salts thereof are important compounds used for various fields such as cosmetics and toiletry goods.
Pyrrolidine carboxylic acid and salts thereof are synthesized by heating for self-cyclization of glutamic acid or a salt thereof. For the reaction, glutamic acid or a salt thereof is directly heated or, upon dissolution or dispersion in water, heated to a high temperature of not lower than the boiling point of water in an autoclave (heating furnace).
For example, DE3735263 discloses a method for producing pyrrolidone carboxylic acid while maintaining the optical activity of glutamic acid, which comprises heating a salt of glutamic acid to produce a salt of pyrrolidone carboxylic acid, and desalting the salt using an ion exchange resin. This method is useful for producing a completely optically active pyrrolidone carboxylic acid salt or pyrrolidone carboxylic acid from an optically active glutamic acid salt. However, in consideration of the aspects of cost and the like, the fact that a fused reaction product solidifies as it cools during the production, making its handling difficult, and the long reaction time (fusion starts in 5 minutes and the reaction ends in 1 hour) described in an example of this patent, this method is not necessarily an advantageous production method to afford high industrial productivity.
JP-b-37-17959 describes a conventional technique comprising heating L-glutamic acid to 190–200° C. for dissolution and removing the resulting water to give pyrrolidone carboxylic acid, and further heating the acid to give ate. As described in this reference, in this method seemingly simple and industrially advantageous, a fused product becomes starch syrup during the reaction and, after cooling, becomes extremely stiff, making handling of the reaction product difficult. This publication discloses, therefore, a production method of DL-pyrrolidone carboxylic acid, which comprises heating 1 part of a D-isomer or L-isomer of glutamic acid, or DL-glutamic acid in an autoclave (heating furnace) with 0.5–15 parts of water to produce a D-isomer or L-isomer of pyrrolidone carboxylic acid in the early stage of reaction, continuing heating to give a racemate, and precipitating and separating crystals.
JP-A-51-110559 discloses a method for obtaining an aqueous solution of a salt of pyrrolidone carboxylic acid, which comprises heating a mixture of glutamic acid and a salt thereof in water under pressurization in an autoclave (heating furnace) and, after completion of the reaction, neutralizing the reaction mixture.
For the production of pyrrolidone carboxylic acid and a pyrrolidone carboxylic acid salt, a method comprising directly heating glutamic acid or a salt thereof without a solvent is known, but in consideration of difficult handling of the fused reaction product, a method comprising reaction in an aqueous solution or aqueous dispersion of glutamic acid or a salt thereof in an autoclave (heating furnace) under the vapor pressure has been actually employed.
From the aspect of industrial production, however, a reaction in an autoclave is not fully satisfactory for producing pyrrolidone carboxylic acid in a short time at a high reaction rate and higher production efficiency.
In addition, JP-A-11-342379 discloses production of various organic acids by hydrolysis of protein in fish meat with subcritical water, which produces pyrrolidone carboxylic acid as well.
However, the reaction mixture obtained by the method described in this publication contains many other amino acids and organic acids. When efficiently producing pyrrolidone carboxylic acid having a high purity, therefore, respective unit operations, such as separation by ion exchange resin and membrane and crystallization, are essential and this method is not effective.